Restricting sleep on week days and catching up on sleep over the weekend is an extremely common pattern among both working and school populations, and is one that can persist for decades. Many people believe that they habituate to this recurrent pattern of sleep restriction, and that sleeping in on the weekends (i.e., obtaining 'recovery sleep') fully restores any sleep lost during the week. However, there is currently no evidence to support this hypothesis, and it remains unknown how systems involved in the stress response (e.g., the hypothalamic-pituitary-adrenal [HPA} axis, the sympatho-adrenal system, and the inflammatory system) react to these recurrent sleep loss and recovery patterns. Sleep loss is a significant and unique physiological stressor, as sleep itself is a biological resource necessary to regulate and maintain various physiological systems. As dysregulation of stress response systems is associated with a broad range of disease states, it is important to understand how these systems are affected by these commonly observed sleep patterns. Specifically, does the stress response become habituated and show a decreased response to repeated episodes of sleep restriction and recovery sleep, or does it become sensitized and exhibit an increased response? There also remains a question of whether the time generally allotted for recovery sleep (i.e., weekend nights) is sufficient to recover from the sleep debt accumulated during the week. Little is known about recovery from any type of sleep loss;however, preliminary data suggests that there may be a dissociation of biological and subjective recovery even from single episodes of sleep loss. We propose to investigate the effects of repeated exposure to sleep loss using a 23-day in-hospital protocol with three cycles of five days sleep restricted to 4 hours per night followed by two days of recovery sleep, thus closely resembling a real-life sleep restriction-recovery pattern experienced by many in the general population. We will study response patterns of HPA, sympatho-adrenal, and inflammatory systems, as well as subjective mood and pain ratings, both between and within episodes of sleep restriction. We will also test a potential mechanism of sensitization: impaired sensitivity of monocytes to the anti-inflammatory effects of cortisol. Results from this research will provide critical insights into the question of whether common patterns of recurrent sleep restriction and recovery compromise the integrity of stress response systems, thereby increasing susceptibility to a variety of diseases including cardiovascular, mood- and pain-related disorders. PUBLIC HEALTH RELEVANCE: This proposal investigates the consequences of repeated episodes of restricted sleep followed by recovery sleep, on the body's stress systems. These sleep patterns are commonly observed in the general population, where sleep time is reduced on weeknights and extended on weekends, but we know little about the physiological and psychological consequences. Findings from this proposed research will provide the first evidence of whether these patterns of sleep restriction and recovery elevate stress and inflammatory indicators of increased risk for the development of cardiovascular, mood- and pain- related disorders.